Is AMPD3 p.Tyr558= (c.1674C>T) pathogenic?

AMPD3 p.Tyr558= (c.1674C>T) is classified Likely benign in AMPD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Common (popmax 5.28%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.Tyr558= (c.1674C>T)?

AMPD3 p.Tyr558= (c.1674C>T) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

AMPD3 p.Tyr558=

Q: How common is AMPD3 p.Tyr558= (c.1674C>T) in the general population?

AMPD3 p.Tyr558= (c.1674C>T) is common (popmax 5.28%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1674C>T · rs114718879 · VCV879069

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.28%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Erythrocyte AMP deaminase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.53, phastCons 1
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.28% Middle Eastern · 320/6,062 alleles

Filtering AF 4.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.62%

Overall 2.44% 39,437/1,614,206 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.28%	19
Finnishnot grpmax-eligible	4.31%	23
Ashkenazi Jewishnot grpmax-eligible	2.84%	35
European (non-Finnish)	2.69%	37
Remaining individualsnot grpmax-eligible	2.5%	40
Admixed American	1.74%	57
Amishnot grpmax-eligible	1.21%	83
South Asian	0.933%	107
African / African-American	0.406%	246
East Asian	0.00446%	22,446

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AMPD3
Protein: p.Tyr558=
Coding: c.1674C>T
MANE Select: NM_001025389
dbSNP: rs114718879
Type: single nucleotide variant
Location: chr11:10500202 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74

Full AMPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Erythrocyte AMP deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMPD3 c.1135-5C>A Uncertain significance ★★ same condition
AMPD3 c.1135-6C>G Uncertain significance ★★ same condition
AMPD3 c.1267-3C>T Uncertain significance ★★ same condition
AMPD3 c.*287T>C Uncertain significance ★★ same condition
AMPD3 c.*75C>T Uncertain significance ★★ same condition
AMPD3 p.Ala141= Uncertain significance ★★ same condition
AMPD3 p.Arg426Trp Uncertain significance ★★ ⚠ same condition
AMPD3 p.Arg576= Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ampd3-p-tyr558 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown